Studies designed to determine the sequence of the human genome, as well as studies designed to compare human genomic sequences, have elicited information regarding polymorphisms in the human genome. A wide variety of polymorphisms in the human genome have previously been described. The various types of human genetic polymorphisms include single base substitutions; insertions or deletions; variable numbers of tandem repeats; deletions of all or a large part of a gene; gene amplifications; and chromosomal rearrangements. Generally, polymorphisms that involve a single nucleotide are called single nucleotide polymorphisms (“SNPs”).
Recently, a SNP in codon 16 of the β2 adrenergic receptor gene has been reported and associated with a variation in response to β agonist therapy (Drazen, J M et al, Thorzx, 1996, 51:1168; Liggett, S. B., Am. J. Respir. Crit. Care Med., 1997, 156:S156–62; Martinez, F. D. et al, J. Clin. Invest., 1997, 100:3184–8). Adrenergic receptors are hormone receptors on the surfaces of various cells. When bound to an adrenergic receptor site, a hormone can trigger a cascade of cellular events. Hence, adrenergic receptors and the hormones that bind to them, in large part form the mechanism that controls cellular events at a molecular level. Many pharmacological compounds mimic molecules that bind to adrenergic receptor sites and, in this manner, clinically regulate cellular function. For example, a class of drugs known as beta-agonists bind to β2 adrenergic receptor sites and are widely used as a medication for aesthma. Individuals with a SNP in codon 16 of the β2 adrenergic gene, however, may not respond to such therapies do to a conformational, or other, change in the receptor that causes a decrease in the affinity between the receptor and the medication or hormone.
It would therefore be advantageous to provide a means for detecting the polymorphism in codon 16 of the β2 adrenergic receptor gene prior to prescribing medications that would not be efficacious as a result of the polymorphism.